This invention is related to peptide substances extracted from the brains of estivating lungfish Protopterus annectens (Owen) and a process of producing same, and to a method of decreasing oxygen consumption and effecting hypothermia in animals. More particularly, this invention relates to novel hormone-like peptides and homologs and analogs thereof possessing an antimetabolic activity, and to the use of these peptides for their biological activity.
The lungfish, which estivates in the dry season, has the capacity to survive in a state of deep torpor for an uninterrupted period of more than two years.
Most of the previous investigations on lungfish have been conducted on the African lungfish Protopterus aethiopicus found in Lake Victoria, Africa. It has been found that the brain extracts from these estivating lungfish were capable of inducing torpor, metabolic supression, and hypothermia when injected intravenously into a test non-torpidator. The brains of estivating Protopterus aethiopicus were treated with acetic acid to form the biologically active extract. See Swan, et al., Amer Naturalist, 103(931): 247-257 (1969). However, it is noted that the lungfish used in this study were induced into estivation artificially. Furthermore, these lungfish belonged to a species different from that of the present invention.
It has been discovered by the present inventor that the brain extracts from estivating lungfish Protopterus annectens (Owen) found in Tchad, Africa, possess biological activity. This has been described in the inventor's prior applications mentioned above, especially Ser. No. 082,738.
The prior application discloses that a crude brain extract from estivating Protopterus annectens can be prepared by extracting with acetic acid and that the crude extract can be refined by subjecting the extract to successive gel and ion exchange chromatography steps.
Further work by the inventor has resulted in the isolation of a pure peptide having antimetabolic activity in animals and the ability to reversibly suppress synthesis of DNA and protein biosynthesis in in vitro tests. The additional purification was accomplished by successive high pressure liquid chromatography steps following the ion exchange chromatography.